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Biomedical subjects

T Kuroda

Publications and source records attributed to T Kuroda.

At least 181 records · Page 10Linked to original sources

Mutational analysis of amiloride sensitivity of the NhaA Na+/H+ antiporter from Vibrio parahaemolyticus.

The activity of the NhaA Na+/H+ antiporter of Vibrio parahaemolyticus is inhibited by amiloride. We found an amino acid sequence in the NhaA that was identical to a putative amiloride binding domain of the Na+/H+ exchanger in mammalian cells. We constructed mutant NhaAs that had amino acid substitutions in the putative amiloride binding domain by site-directed mutagenesis. These include V62L (Val62 replaced by Leu), F63Y, F64Y, and L65F. Most mutant NhaAs showed decreased sensitivity for amiloride. Among these, the F64Y mutant NhaA showed the least amiloride sensitivity, with a Ki value 7 to 10 times greater than that in the wild type. Thus, the sequence between residues V62 and L65 in NhaA, especially F64, is very important for the inhibitory effect of amiloride on the antiporter.

Amiloride↗

Influence of diet on the single-dose pharmacokinetics of isosorbide 5-mononitrate and sustained-release isosorbide dinitrate.

The influence of diet on the single-dose pharmacokinetics of isosorbide 5-mononitrate (IS-5-MN) and sustained-release isosorbide dinitrate (ISDN) was studied in 8 healthy male volunteers. The subjects received either a low-calorie/low-fat diet (LCFD) or a high-calorie/high-fat diet (HCFD) according to a cross-over schedule and were administered the drug in tablet form after breakfast. The study was conducted first in 8 subjects who received a 20 mg IS-5-MN tablet and then in 6 of these individuals who received a 20 mg sustained-release ISDN tablet. After oral doses of IS-5-MN, the plasma drug levels declined monoexponentially and could be described by a one-compartment open model. There were no significant differences in the pharmacokinetic parameters for IS-5-MN between the LCFD and the HCFD. After administration of sustained-release ISDN, the plasma ISDN levels showed marked variations both between and within individuals. The increase in the mean AUC0-12 values for ISDN with the HCFD was found to exceed 60%, although there was no significant difference between the two diets.

Administration, Oral↗

Na+(Li+)/H+ antiporter in Pseudomonas aeruginosa and effect of Li+ on cell growth.

Everted membrane vesicles were prepared from cells of Pseudomonas aeruginosa, and cation/H+ antiport was measured. We observed activities of Na+/H+ antiport, Li+/H+ antiport and K+/H+ antiport. Judging from the competition pattern, it seems that there are at least two types of antiporter, a Na+(Li+)/H+ antiporter and a K+/H+ antiporter. Na+ was a good substrate for the Na+(Li+)/H+ system, whereas Li+ was a poor substrate. Although the K(m) value for Na+ (or Li+) was similar to those in Escherichia coli Na+/H+ antiporters, the Vmax value for Na+ (or Li+) was much smaller in the P. aeruginosa antiporter than in the E. coli antiporters. Growth of P. aeruginosa was strongly inhibited by 0.4 M LiCl, but not by NaCl or KCl.

Amiloride↗

Synthesis and hypolipidemic activity of diesters of arylnaphthalene lignan and their heteroaromatic analogs.

A series of diesters of arylnaphthalene lignan and their heteroaromatic analogs were synthesized and evaluated for hypolipidemic activity. The disasters with modifications at C-3 showed excellent hypocholesterolemic and high-density lipoprotein (HDL) cholesterol-elevating activities. Structure-activity analysis indicated that the 2-pyridylmethyl ester 5l has the optimum activity.

Animals↗

Sarcoid reaction in thyroid diseases: report of a case of thyroid carcinoma demonstrating sarcoid reaction in regional lymph nodes.

We describe an extremely rare case of thyroid carcinoma accompanied by sarcoid reaction in regional lymph nodes. The patient, a 40-year-old woman, was found to have anterior neck swelling during a routine medical examination. Physical examination revealed a bad movable and firm nodule measuring 3.5 x 2.5 cm in the right thyroid lobe. Examination of a fine-needle aspiration cytology of the nodule suggested papillary carcinoma of class V. Right lobectomy and isthmectomy with neck dissection were performed. Histopathological examination of the resected specimens revealed papillary carcinoma accompanied by metastatic foci in right perithyroidal lymph nodes and non-caseous sarcoid-like granulomas in pretracheal, right upper internal deep cervical and submandibular lymph nodes. We concluded that these granulomas were due to a sarcoid reaction associated with thyroid carcinoma, after performing examinations to rule out the possibility of systemic sarcoidosis.

Adult↗

Freeman-Sheldon syndrome: case management from age 6 to 16 years.

OBJECTIVE: This is the first description of long-term follow-up of a case of Freeman-Sheldon syndrome. Microstomia was treated with a mouth expander for 2 to 3 hours per day before active orthodontic treatment. Separate impressions were necessary in each quadrant of both upper and lower jaws because of limited mouth opening. CONCLUSION: Orthodontic treatment improved the patient's Class II malocclusion, which was accompanied by crowding and a deep bite.

Adolescent↗

A patient with acromegaly who showed remarkable improvement of hyperglycemia after treatment with octreotide.

A case with diabetes mellitus associated with growth hormone (GH)-producing pituitary adenoma is described. A 56-year-old woman who had been treated for diabetes mellitus for 3 years, was admitted for the treatment of hyperglycemia. She showed a few acromegalic features and her plasma GH level was 146 +/- 16 ng/ml. After improvement of plasma glucose level by insulin injection, octreotide therapy (100 micrograms/8 hours) was started. Seven days after the initiation of octreotide therapy, the fasting plasma glucose level was almost normalized without insulin injection. After the octreotide treatment, urinary C-peptide excretion was significantly decreased and the plasma GH level became within normal range. In this case, octreotide appears to have improved the insulin sensitivity by reducing the plasma GH level.

Acromegaly↗

Three-dimensional computed tomography imaging of a frontal skull base fracture.

A 7-year-old boy presented with recurrent meningitis after head trauma. Coronal computed tomography (CT) revealed prolapse of the intracranial soft tissue into the right ethmoidal sinus, leading to the diagnosis of right frontal skull base fracture. Three-dimensional CT with bone windows provided a lifelike image of the fracture lateral to the right olfactory groove. This image was most useful in the preoperative planning of the repair surgery.

Child↗

[Study on CAM system for dental model].

The purpose of this study was to introduce our newly-developed CAM system for dental model and to examine the shape reproducibility and measurement reliability of the CAM modelling. The system is composed of a measuring unit, which obtains three-dimensional shape information from the dental model using laser scanning, and an engineering workstation, which creates a three-dimensional graph of the dental model. Output module program which can directly process and output the three-dimensional shape data to the wide use modeling systems was developed as the software of this CAM system. Four different CAM models, that, WAX model, STL model, FDM model, and SL model, were made based on the graph of the dental model taken from a mandibular prognathic patient. The measurement reliability of each CAM model were evaluated using a contact three-dimensional measurement unit. All CAM models except a WAX model demonstrated good shape reproducibility without a blind area, suggesting no problem of the three-dimensional shape data and the output module program. Measurement reliability of each CAM model was 0.12 +/- 0.08 mm in graph, 0.25 +/- 0.05 mm in WAX, 0.28 +/- 0.16 mm in SL, 0.31 +/- 0.15 mm in FDM, and 0.39 +/- 0.18 mm in STL. These results suggested clinical feasibility of this system in accordance with electronic storage of medical information.

Computer-Aided Design↗

[Organ preservation in the treatment of malignant solid tumors in children].

Organ preservation is one of the requirements for maintaining the high quality of life after the treatment of malignant solid tumors in children. We analyze our recent results of renal preservation in the abdominal neuroblastoma and describe 3 cases of successful organ preservation in pelvic malignancy. Between 1982 and 1996, 29 patients with adrenal or retroperitoneal neuroblastoma, that extended into the surrounding tissues and organs and/or to the contralateral side, underwent delayed primary excision. Before 1982, 9 patients were treated and only one ipsilateral kidney was preserved. On the other hand, 13 of 20 kidneys were preserved after 1987. Adoption of cis-platinum deepened our awareness of preserving the kidney. Furthermore, we have altered our strategy since 1987 to continuing preoperative chemotherapy until the size of the tumor becomes as small as it is estimated completely resectable by our own index, which is derived from computed tomography. Kidneys are shielded during intraoperative irradiation, and the tumor relapsed from the shielded area of retroperitoneum in one patient. Four of 14 preserved kidneys became atrophic and lost their function. The bladder and the rectum were left intact at tumor resection after intensive chemotherapy in two patients with pelvic (one retroperitoneal and one vaginal) rhabdomyosarcoma. A yolk sac tumor of the vagina responded completely to chemotherapy with cis-platinum, etoposide and bleomycin. The patient has survived 7.5 years without any local and distant relapse in spite of the fact that surgery, aside from several diagnostic biopsies, was not undertaken.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of recurrent gastric cancer with liver metastasis responding to combination chemotherapy with cisplatin and carmofur].

The patient was a 65-year-old male with recurrent gastric cancer accompanied by metastasis to the liver and distant lymph nodes. He was treated by combination chemotherapy consisting of cisplatin 20 mg/body (day 8-14) and Carmofur 400 mg/body (on consecutive days), in three four-week courses of therapy. After 1 course of administration, the target lesion was reduced in size and the performance status was improved. Generally, a partial response was confirmed by computed tomography (CT). The patient has survived for 8 months in a state of PR. Adverse effects were mild and transient. Though treatment of recurrent gastric cancer with liver metastasis is often ineffective, this case suggests that a combination therapy of cisplatin and carmofur might be effective.

Aged↗

Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy.

Pirfenidone (PFD) is a new compound that prevents and even reverses the extracellular matrix accumulation in several organs as shown by experimental and clinical studies. In the present study, we examined the effect of PFD (500 mg/kg daily in the food) on the progression of chronic renal failure (CRF) in the 5/6 nephrectomy rat model. Proteinuria progressively increased in rats with renal ablation (C) at 12 weeks. Urinary protein excretion in PFD-treated rats (P) was numerically lower than C, but the difference did not reach statistical significance. In contrast, in the chronic phase, PFD improved renal function and reduced collagen accumulation detected by hydroxyproline content (OH-Pro) in the cortex of the remnant kidney. Although creatinine clearance decreased with time in C, the values in P were significantly better at 10 and 12 weeks. The OH-Pro in C at 12 weeks was significantly higher than that of no-ablation, sham-operated rats, whereas OH-Pro in CRF was lower in (P). Expression of mRNA for type IV and I collagen in the cortex also increased in C, but it was inhibited in (P). To study the role that TGF-beta plays in the regulatory process following CRF, we examined the expression of TGF-beta mRNA in this model. Levels of cortical TGF-beta mRNA in C were significantly elevated at 12 weeks. The increase was suppressed by PFD. These results demonstrate that PFD attenuates the development of CRF by preventing collagen accumulation in this model, and suggest that PFD can be clinically useful for treating CRF.

Animals↗

Novel selective PDE IV inhibitors as antiasthmatic agents. Synthesis and biological activities of a series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans.

A series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans have been synthesized and evaluated for their ability to selectively inhibit PDE IV isolated from guinea pig. Replacement of the 1-phenyl ring by a pyridone ring led to marked improvement of their selectivity for PDE IV over PDE III. The compounds that were most potent and selective involved those bearing an N-alkylpyridone ring at C-1. These compounds also showed potent antispasmogenic activity without causing significant changes in heart rate in the guinea pig. The most potent compound was 6,7-diethoxy-2, 3-bis(hydroxymethyl)-1-[1-(2-methoxyethyl)-2-oxo-pyrid-4-yl]nap hth alene (17f), ED50 values of histamine-induced and antigen-induced bronchoconstriction in the guinea pig being 0.08 and 2.3 mg/kg iv, respectively. This compound was chosen as a candidate for further pharmacological evaluation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Cloning and sequencing of the gene for Na+/H+ antiporter of Vibrio parahaemolyticus.

A gene encoding an Na+/H+ antiporter was cloned from vibrio parahaemolyticus into the plasmid pBR322 and expressed in Escherichia coli cells. The gene enabled mutant E. coli cells to grow in the presence of 0.2 M NaCl (or 10 mM LiCl). These cells were originally unable to grow under such conditions because of the lack of major Na+(Li+)/H+ antiporters. We detected Na+/H+ antiporter activity due to the gene in membrane vesicles. The gene was sequenced and the deduced amino acid sequence was found to be 72% identical to the NhaB Na+/H+ antiporter of E. coli.

Amino Acid Sequence↗

Multiple myeloma-associated systemic vasculopathy due to crystalglobulin or polyarteritis nodosa.

Systemic vasculopathy is a rare complication of multiple myeloma (MM). We describe a patient diagnosed with MM who developed clinical features of systemic vasculopathy including gangrene, livedo reticularis, hypertension, renal failure, and perforation of the small intestine. Histopathologic examination of the small intestine revealed necrotizing vasculitis in the small arteries, along with crystalline deposits in the small vessels. To our knowledge, previously reported cases of systemic vasculopathy associated with MM include at least 9 cases due to crystalglobulin deposition in vessels and 2 due to polyarteritis nodosa. Deposits of crystalglobulin may have induced systemic necrotizing vasculitis in our patient.

Adult↗

High prevalence of serum apolipoprotein E4 isoprotein in rheumatoid arthritis patients with amyloidosis.

OBJECTIVE: To determine whether serum Apolipoprotein E (Apo E) type 4 isoprotein is a risk factor for the development of amyloidosis in patients with rheumatoid arthritis (RA). METHODS: Using isoelectric focusing, we studied Apo E phenotype expression and the corresponding allele frequencies (epsilon 2, epsilon 3, and epsilon 4) in 35 patients with RA and amyloidosis, 65 patients with RA and without amyloidosis, and 63 healthy controls. RESULTS: The Apo E3/4 phenotype was significantly more common in the group with amyloidosis (31.4%) than in the patients without amyloidosis (12.3%; P < 0.05) or in healthy controls (12.7%; P < 0.05). The frequency of the epsilon 4 allele was significantly greater in the group with amyloidosis (0.16) than in the patients without amyloidosis (0.07; P < 0.05) or in healthy controls (0.07; P < 0.05). CONCLUSION: The presence of Apo E4 isoprotein may be a risk factor for the development of amyloidosis in patients with RA.

Adult↗